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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Apr;114(7):1351–1358. doi: 10.1111/j.1476-5381.1995.tb13355.x

Selective modification of rat hepatic microsomal fatty acid chain elongation and desaturation by fibrates: relationship with peroxisome proliferation.

M Alegret 1, E Cerqueda 1, R Ferrando 1, M Vázquez 1, R M Sánchez 1, T Adzet 1, M Merlos 1, J C Laguna 1
PMCID: PMC1510293  PMID: 7606338

Abstract

1. The time-course of the effect of clofibrate (CFB), bezafibrate (BFB) and gemfibrozil (GFB) on lipid plasma levels and palmitoyl-, palmitoleoyl- and gamma-linolenoyl-CoA elongase, delta-9, delta-6 and delta-5 desaturase activities, and microsomal electron transport chains, as well as the correlation with the peroxisomal proliferation phenomenon have been studied in male Sprague-Dawley rats. 2. As reported in our previous work, the three drugs behave as peroxisomal proliferators (the order of potency was BFB > CFB > or = GFB) and induced a clear reduction in both plasma cholesterol and triglyceride levels. 3. Palmitoyl-CoA elongation activity was increased by the three drugs (BFB = GFB > CFB), whereas palmitoleoyl-CoA elongation activity was only enhanced by GFB. Elongation activity was not modified by fibrates when gamma-linolenoyl-CoA was used as substrate. These results are in accordance with the existence of three different elongation systems for saturated, mono- and polyunsaturated fatty acids. 4. delta-9, delta-6 and delta-5 desaturase activities were increased by the three fibrates, with an order of potency BFB > CFB = GFB for delta-9 and delta-5, and GFB > BFB = CFB for delta-6. 5. Of the enzyme activities integrated in the microsomal electron transport chains, NADH cytochrome b5 reductase was not affected by fibrate treatment, NADPH cytochrome c reductase activity was enhanced (BFB = GFB > CFB), whereas NADH cytochrome c reductase activity was reduced by CFB and BFB.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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